STRUGGLING with DEPRESSION, ANXIETY, or BIPOLARITY? LEARNING can really HELP. Start with ARTICLES above or Topics below. Ty! Bill

L-methylfolate for Depression? “Never heard of it!”

When was the last time you had the audacity to tell your primary care physician or psychiatrist what you wanted to try? L-methylfolate for depression might make your list.

L-methylfolate (MTHF), a medical food, is being used for the treatment of depression. It’s especially effective as an antidepressant add-on in the early stages of treatment.

Let’s dig in.

Updates!!! When you’re finished reading the article, be sure to click here for an important update. Actually, by now (June 8, 2011), there are several informative updates in the comment section – especially if you’re a European reader. Click the link!

What the Heck is L-methylfolate?

Folic acid is a form of Vitamin B9. Naturally occurring, it’s known as folate. Folic acid itself is not biologically active. It’s the products of its conversion to dihydrofolic acid that are crucial to our functioning.

Interestingly, folic comes from the Latin, folium, meaning leaf. It makes sense, then, that leafy vegetables are a primary source, along with fortified cereals and breads.

L-methylfolate (actually, L-methylfolate2) is a form of folate. And it’s the only form that crosses the blood-brain barrier.

By the way, the blood-brain barrier is a need-to-know kind of thing. I wrote an article not long ago on melatonin, which included a nice explanation of the blood-brain barrier. Click here for a look-see.

In the USofA, MTHF (aka Deplin) is marketed under the FDA classification, medical food. It’s available by prescription only, and it’s thought to be safe with very few side effects, if any.

And it’s sure a lot less expensive that the add-on meds Big Pharma would like you to use.

And This is Important Because?

Some of us come into this world with a genetic boo-boo that leaves us at high-risk for a folate deficiency. A folate deficiency may increase the risk of depression, as well as reduce the action of antidepressants. And that’s because folate provides regulatory assistance to the neurotransmitters associated with depression.

Guess what? Approximately 70% of those enduring major depressive disorder have a genetic error that results in an imbalance of L-methylfolate2.

So Why Don’t I Pop Folic Acid Tabs?

Folate is an essential vitamin, which means we need it, but can’t produce it naturally. Folic acid is the synthetic form of folate found in vitamin supplements. It’s also the synthetic form found in prescriptions for higher doses for medical use. Under normal circumstances, folic acid has problems delivering adequate MTHF levels to the brain.

Using MTHF solves that problem.

Confirmed by Research

The results of a study, authored by Dr. Lawrence D. Ginsberg of Red Oak Psychiatry in Houston, were published last month in Innovations in Clinical Neuroscience.

The study confirmed that L-methylfolate (Deplin) is a powerful supplement. When used in combination with antidepressants in the early treatment of depression, major and more rapid improvement was noted – versus using an antidepressant alone.

And it was especially helpful with treatment resistant cases.

Ever see those Abilify and Seroquel TV ads? They’re atypical antipsychotics being touted as antidepressant add-ons for use in treatment resistant depression. Hopefully, Dr. Ginsberg’s findings will kick a dent in that effort.


I wanted to accomplish two things in this piece. Certainly, I wanted to make you aware of L-methylfolate. But I also want to encourage you to take such subjects to your primary care physician and/or psychiatrist for discussion. It’s an integral part of managing our health care.

I mean, we’re all likely comfortable that our physician and/or psychiatrist knows about, say, desvenlafaxine (Pristiq) for the treatment of depression. But would any of us bet he/she would know about L-methylfolate? Hard to say.

So there they are – L-methylfolate and taking command of our health care. Nice.

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  • Jim

    Wow. Could not have said it better ourselves. Nice job on doing your homework and capturing the full flavor of the topic. Consider me a “fan”. should you wish to discuss any further. Jim

    • Sure appreciate your visit and comment, Jim. I’m all for having “fans.” I took a quick look at Will spend some quality time on it tonight. Stop by again!

  • Thanks for taking the time to discuss this, I feel strongly about it and love learning more on this topic. If possible, as you gain expertise, would you mind updating your blog with more information? It is extremely helpful and beneficial to your readers.

    • Thank you for your visit and comment. chipur readers – the site link the reader provided leads to Bible Health. The featured article is all about symptoms of depression. Worth a look see. I appreciate the tip on updating chipur with more info. I’m on it – and thank you.

  • Does anybody know where in Canada I can fill my prescription for L-methyl folate?

    • Hi Cathy!
      Wish I could come up with some answers for you. After spending a good bit of time researching the matter, I came up empty-handed. I already knew L-methylfolate (Deplin) was available in the US only; however, I thought there might be an angle. Sure doesn’t appear to be. Thank you for visiting Chipur and commenting…

    • Michael Dowdy

      Hello Cathy. I’m in the USA and I’m still learning about this. You may try to visit health food stores or even look on Amazon if you’re unable to find Deplin or Metanx there in Canada. Another name for them is methylated or activated vitamins and folic acid. If you haven’t tried them yet don’t get too alarmed if really strange feelings, thoughts, and sensations happen. If your body all at once starts purging itself of toxins (because of increased glutathione production?) it will show up in your urine. I have not found out why when about 24 hours of dosing my urine felt very hot, unlike a UTI, but similar. I still don’t know why that happened. It might be too much of the B vitamins, I’m not sure yet. I just began using it five days ago. I almost went to the ER but I changed my mind after some online research. Adverse reactions can happen (and very quickly I might add!) but some of the information I found online said not to be alarmed if it does. I did quickly run to my doctor though! LOL.. If you want you’re welcome to contact me.

      • Great reply to Cathy, Michael. Thank you for your care – in the midst of not feelin’ so hot yourself.

  • Michael Dowdy

    A mutation of the MTHFR gene makes some people, usually of British background, unable to break down amino acids. L methyl folate, activated vitamins, have to be added to the diet so the body can function properly. Somewhat complicated physical and mental processes are severely disrupted and result in early death of individuals afflicted with this genetic defect. Mental illnesses appear including autism and Down’s syndrome. Metanx and Deplin are name brand products of this necessary medication.

    • Thanks, Michael, for the information. So appreciate your visit and participation. Chipur readers, if you’d like more information on the MTHFR gene Michael mentions, here’s a link

  • Michael Dowdy

    Throughout my life (53 years) I’ve had only little success with treating my various symptoms of poor health. Damage is found throughout most of my arteries and systems and I’ve achieved some noticeable help from use of various medications like statins and vascular dilators and vitamins. I’ve had chronic abdominal pain associated with different digestive problems as well as fibrosis of the liver. I’ve tried using oral EDTA with some short-lived success. I’ve just very recently learned that I have two copies of the c677t mutation of the MTHFR gene which is likely the root of most of my problems. Can anyone say with any certainty whether or not that my use of L methylfolate might succeed in reversing the damages caused by this gene mutation and the length of time this may take???

    • Any help for Michael???

  • Patricia Miller

    I can tell you that Deplin has been a truly fantastic addition to my regimine. I take 15 mg once a day and it is fantastic. Since it is a prescription vitamin, my insurance only covers about 1/3 of the cost, making my copy about $80 per month. Worth it to me in the benefit in how I feel.

    • Thanks for you contribution, Patricia. I hope you know how much all you do here is appreciated!

    • Patricia Miller

      I just wanted to update that once I took the 15 mg for two months, I was able to begin cutting the 15 mg pills in 1/2 and take only 7.5 mg and get the same effect. I suspect that once the original deficiency was rectified that my maintenance has been a addressed by the 7.5 mg. I also want to share that on my insurance the cost is the same for a month of 15 mg or a month of 7.5 mg pills. Of course I shared all of this information with my prescribing doctor and psychiatrist and they were glad to continue to support me with the 15 mg prescription. Once every three months I go back to the 15 mg dosage to ensure that I am not “slipping” into a deficient state. I’ve discussed my strategies with my medical/mental health team, and they like my ideas and my rational. Also, I should share that neither of them were familiar with Deplin when I mentioned it, but both were willing to read up and support me when I said I wanted to try it. If you don’t have a medical/mental health team that will treat you like you are a smart member of the team, then it might be time to look for new team mates, in my opinion :-)

  • mbgill

    My insurance wouldn’t cover Deplin anymore and my former doc had no clue about it. It had worked in the past for me but became cost prohibitive. I have MDD with Dysthymic Disorder with major cycles, especially in the spring. My current doc has added Viibriyd to my regimen of Cymbalta, trazadone, and keppra and I’m still having trouble getting out of this cycle. Thanks for this wonderful website – it helps to know I’m not alone.

    • Hi mbgill!

      No doubt, you’re not alone. And I/we sure appreciate your participation. Thank you for the kind words, as well.

  • Michael Dowdy

    Here is a copy of part of a letter to one of my family members. I hope others may benefit. I’m not a doctor or professional and my information is from my personal experience. My depression problem also seems to have eased some. Here it is: It seems you and I have very similar health problems. I may have found a
    key part that we’re missing. Some of the Dowdy’s have the MTHFR gene
    mutation. It’s a pretty common problem to much of earth’s population.
    Mine’s a little different since I have two copies meaning that I got the
    mutation from both of my parents. I’ve done a lot of research and I may
    have found an important, yet simple key to solving the problem. My
    blood work came back normal, actually good, for the first time in close
    to thirty years. MTHFR is a metabolism problem. Methylation is a key
    essential part of our metabolism. There is an apparent way to overcome
    the problem by helping the missing or damaged methylation function. My
    system lacks the ability to efficiently methylate, since my system does
    not produce sufficient methionine synthase, the addition of a methyl
    donor is needed. There is an inexpensive supplement called TMG
    (trimethylglycine) which is a methyl donor. Don’t confuse
    trimethyglycine with dimethylglycine though. I think I read somewhere
    that Betaine HCL is a little different than TMG but I’m not certain.
    TMG fixes most of the problem with homocystiene while at the same time
    boosting the body’s immune system, promoting liver health and repair,
    and reducing inflammation in the rest of the digestive system. I’ve
    actually seen improvement in my neuropathy and my memory seems better
    and quicker. I’ve also added needed activated vitamins including folate
    prior to the addition of the TMG. I hope the TMG might do sufficiently
    on it’s own but for now I’m still going to add the methylated vitamins
    and folate at this early stage since my blood work has improved significantly, if not completely.
    Glutathione production and use is dependent on a working methylation
    pathway, key to our body’s immune system function. In short, try
    carefully adding TMG to your diet and see if you find improvement. And always talk to your doctor about changes you’d like to try.

  • Dr Ram Arora


  • Shana

    Hello! I am a third year pharmacy student at Wingate University in North Carolina, and I happen to be doing a presentation on l-methylfolate for our CAM (complementary and alternative medicine) class. I am unable to locate your resources used for this article and was hoping you could help me out?
    You did a Great job reviewing the supplement! even to be recognized by the manufacturer and given only good praises!? Very Nice Work!
    Thanks, Shana